Solid dispersion system with delayed release of zaltoprofen by kneading
The kneading process with hydrophilic polymers transforms zaltoprofen into an amorphous form, enhancing solubility and achieving controlled release, addressing solubility and bioavailability issues in conventional formulations, suitable for industrial production.
Patent Information
- Application Number
- DE202025107019
- Authority / Receiving Office
- DE · DE
- Patent Type
- Utility models
- Current Assignee / Owner
- Filing Date
- 2025-11-15
- Publication Date
- 2026-01-08
- Estimated Expiration
- 2035-11-30
AI Technical Summary
Conventional formulations of zaltoprofen, a nonsteroidal anti-inflammatory drug, face challenges due to low water solubility, slow dissolution rate, and reduced oral bioavailability, leading to frequent dosing and gastrointestinal irritation, while existing solid dispersion methods are complex, costly, or unsuitable for large-scale production.
A kneading process using hydrophilic polymers like poloxamer-188 and HPMC converts zaltoprofen to an amorphous form, improving solubility and achieving delayed release through a uniform distribution within a hydrophilic polymer matrix, suitable for industrial production without harmful solvents.
The system enhances zaltoprofen's solubility and dissolution, provides controlled release over 12 hours, reduces dosing frequency, and minimizes gastrointestinal side effects, ensuring therapeutic consistency and patient compliance.
Abstract
Description
Field of invention
[0001] The invention relates to a system for producing a solid dispersion of zaltoprofen with delayed drug release by kneading with hydrophilic polymers to improve solubility and controlled drug release. Background of the invention
[0002] Zaltoprofen is a nonsteroidal anti-inflammatory drug (NSAID) known for its therapeutic efficacy, but limited by its low water solubility, slow dissolution rate, and reduced oral bioavailability. These limitations often necessitate frequent dosing, leading to poor patient compliance and an increased risk of gastrointestinal irritation. Conventional formulation approaches do not significantly improve solubility or achieve sufficient release profiles for optimized therapeutic effect. Solid dispersion techniques have proven to be promising strategies for improving the solubility of poorly water-soluble drugs; however, many existing methods are technically complex, costly, or unsuitable for large-scale production.Kneading technology offers a simple and environmentally friendly approach, but requires optimization to improve solubility and achieve delayed drug release. Hydrophilic polymers such as poloxamer-188 and hydroxypropyl methylcellulose (HPMC) have shown potential to improve water solubility and modulate release kinetics. Therefore, there is a need for an optimized system to produce a stable, amorphous solid dispersion of zaltoprofen with delayed release and improved therapeutic efficacy. Summary of the invention
[0003] The invention provides a system for producing a delayed-release solid dispersion of zaltoprofen. This system is based on a kneading process and contains hydrophilic polymers such as poloxamer-188 and hydroxypropyl methylcellulose. The system enables the conversion of zaltoprofen from its crystalline to an amorphous form during kneading, thereby significantly improving its water solubility and dissolution properties. Through controlled mixing, wetting, and incorporation of the polymers, the system ensures a uniform distribution of the drug molecules within the hydrophilic polymer matrix.
[0004] Delayed drug release is achieved by integrating release-modifying polymers into the amorphous dispersion, enabling gradual drug diffusion over a 12-hour period. This system simplifies manufacturing, reduces processing costs, and eliminates the need for environmentally harmful solvents, making it suitable for industrial production. By combining improved solubility and controlled release, the invention offers a formulation that reduces dosing frequency, minimizes gastrointestinal side effects, and improves overall patient compliance. Detailed description
[0005] The system includes a kneading unit for the production of zaltoprofen solid dispersions with hydrophilic polymers. The active ingredient and selected polymers, such as poloxamer-188 and HPMC, are placed in the kneading chamber and mixed there under controlled pressure and hydration. The kneading process promotes uniform wetting and the interaction of the polymers with the active ingredient molecules, thus supporting the transition of zaltoprofen into an amorphous state.
[0006] During the kneading process, the hydrophilic polymer matrix improves the wettability of zaltoprofen, increases its surface area, and enhances its water solubility. Controlled mechanical shear and hydration ensure a homogeneous distribution of the active ingredient within the polymer network, prevent recrystallization, and stabilize the amorphous form.
[0007] The system allows for adjustment of the polymer ratios, kneading time, and moisture content to achieve optimal dispersion properties. Poloxamer-188 contributes to micellar solubilization, while HPMC forms a hydrophilic matrix that enables prolonged drug release. This combination ensures both improved solubility and controlled diffusion.
[0008] The kneaded mass is then dried and ground to obtain free-flowing granules suitable for encapsulation or compression. The drying step stabilizes the amorphous state and prevents moisture-induced recrystallization. Grinding ensures a uniform particle size distribution, thus improving subsequent processing properties.
[0009] Following administration, the solid dispersion rapidly increases the solubility of zaltoprofen through improved wettability and polymer-assisted dispersion. The hydrophilic polymers gradually swell in the gastrointestinal fluids, forming a gel-like matrix that modulates drug diffusion and prolongs release for up to 12 hours.
[0010] This delayed-release formulation reduces fluctuations in plasma concentration, thus minimizing the gastrointestinal irritation often associated with NSAIDs. The controlled-release system therefore improves therapeutic consistency and patient adherence by reducing the frequency of dosing.
[0011] The system relies on environmentally friendly, solvent-free processing and avoids harmful organic solvents commonly used in conventional solid dispersion processes. The kneading technique ensures scalability, making the invention suitable for industrial production.
[0012] Overall, the invention offers a robust, economical, and scalable system for the production of delayed-release zaltoprofen dispersions. This improves solubility, dissolution, and the overall therapeutic effect.
Claims
[1] A system for the production of delayed-release zaltoprofen dispersions comprising a kneading unit that mixes the drug with hydrophilic polymers to form an amorphous dispersion. [2] System according to claim 1, wherein the hydrophilic polymers comprise Poloxamer-188 and hydroxypropylmethylcellulose to improve solubility and prolong drug release. [3] System according to claim 1, wherein the kneading parameters, including mixing time, degree of hydration and polymer ratio, are controlled such that the amorphous form of zaltoprofen is stabilized. [4] An oral delayed-release formulation containing the solid dispersion produced according to claim 1 and enabling improved solubility and controlled release over up to 12 hours.